[Strategies for improved healthcare of people with the endemic disease rheumatism exemplified by rheumatoid arthritis]. / Strategien zur verbesserten Versorgung von Menschen mit der Volkskrankheit "Rheuma" am Beispiel der rheumatoiden Arthritis.

New therapeutic principles and considerable diagnostic advances have made it possible to define different rheumatic diseases and especially rheumatoid arthritis (RA) at an early stage and by starting an early and aggressive medication a considerable proportion of patients with RA will reach the status of low disease activity or even remission. With the additional development of composite measures to estimate the disease activity of RA, it was the goal of an international working group consisting of rheumatologists and patients to develop recommendations for treating rheumatoid arthritis in a similar way as for patients with hypertension or diabetes, with the aim to achieve remission as often as possible. This treat-to-target initiative has taken off in quite a number of different countries including Germany leading to discussions on how this initiative can be integrated into the specific national healthcare systems and what possibilities would exist for its implementation. To develop strategies for an improved healthcare of people suffering from rheumatic diseases and using RA as an example, action elements and postulates were developed which will be discussed in more detail in the present manuscript.

Subjective quality of life and sexual functioning after germ-cell tumour therapy.

PURPOSE: To evaluate the influence of germ-cell tumour therapy on sexual functioning and subjective quality of life (QL). To investigate the communication about sexual problems between patients, their partners, and doctors. In all, 474 patients treated for germ-cell tumours at the Department of Internal Medicine III, Ludwig-Maximilians-University Munich, from 1979 to 2000 were asked to complete a self-report questionnaire concerning psychosocial dimensions and subjective QL (QLS; Henrich and Herschbach, 2000). In total, 341 patients returned a completed questionnaire (response rate, 71.9%). The median age at survey was 41.9 years and the median follow-up period after therapy was 9.6 years. Persisting sexual sequelae were lower than in the current literature: decreased sexual desire (7.1%), erection (10.0%), orgasm (10.2%), ejaculation (28.8%), sexual activity (8.5%), and sexual satisfaction (4.8%). In QL the satisfaction with 'friends/acquaintances' (P<0.001) and 'family life/children' (P<0.001), is lower than in the healthy population. Correlations between functional scales and subjective QL were highly significant. There is a strong correlation between sexual satisfaction and global life satisfaction (Spearman's Rho: 0.48; P<0.01). A total of 61.4% of patients were not offered communication about sexual problems by their doctors and 21.2% were unable to talk with their partner about sexual issues. In conclusion, moderating psychosocial variables (e.g. personality factors, cognitive processes) should be investigated to clarify the relationship between life satisfaction (subjective QL) and functional impairments. Communication about sexual problems should be offered as a standard to patients treated for germ-cell tumours.

The long-term psychosocial effects of haematopoetic stem cell transplantation.

The purpose of this study was to identify long-term psychosocial effects of allogenic, syngenic and autologous haematopoetic stem cell transplantation (HSCT) on relevant parameters (physical performance, role and sexual functioning, intimate relationships, professional and social rehabilitation). A total of 163 patients, who had undergone an autologous (11.6%), syngenic (3.1%) or allogenic (85.3%) HSCT at the Department of Internal Medicine III, Ludwig-Maximilians-University, during a preceding 16-year period, were asked to complete the Herschbach Questionnaire on Stress in Cancer Patients in order to evaluate their current psychosocial distress status. An additional questionnaire for demographic data was used. Reduced quality of life as a result of HSCT is restored to its pre-HSCT level by most patients within 2 years after transplantation (no differences between groups transplanted 2-5, 6-9 or >10 years ago). The majority of patients had serious problems with "fitness" (24%), followed by problems with "pain" (17.2%) and "fear/emotional stress" (14.1%). Professional reintegration is an important factor in patients' well-being. However, 30.7% of these patients did not return to work at all. Unemployed patients had significantly higher scores for pain, anxiety, sleep disorders, depression, impairments in social functioning, partnership and family life. Only 9.8% of all patients took part in a psychotherapeutic programme and 39.3% in a rehabilitation programme. Identifying strategies for risk patients (e.g. lower education and married) need to be developed in order to optimize support for this group. Although some patients show a higher distress score in anxiety/fear and psychophysical performance, only 9.8% of all patients took advantage of available psychotherapy.

Agonistic and antagonistic properties of progesterone metabolites at the human mineralocorticoid receptor.

OBJECTIVE: Progesterone binds to the human mineralocorticoid receptor (hMR) with nearly the same affinity as do aldosterone and cortisol, but confers only low agonistic activity. It is still unclear how aldosterone can act as a mineralocorticoid in situations with high progesterone concentrations, e.g. pregnancy. One mechanism could be conversion of progesterone to inactive compounds in hMR target tissues. DESIGN: We analyzed the agonist and antagonist activities of 16 progesterone metabolites by their binding characteristics for hMR as well as functional studies assessing transactivation. METHODS: We studied binding affinity using hMR expressed in a T7-coupled rabbit reticulocyte lysate system. We used co-transfection of an hMR expression vector together with a luciferase reporter gene in CV-1 cells to investigate agonistic and antagonistic properties. RESULTS: Progesterone and 11beta-OH-progesterone (11beta-OH-P) showed a slightly higher binding affinity than cortisol, deoxycorticosterone and aldosterone. 20alpha-dihydro(DH)-P, 5alpha-DH-P and 17alpha-OH-P had a 3- to 10-fold lower binding potency. All other progesterone metabolites showed a weak affinity for hMR. 20alpha-DH-P exhibited the strongest agonistic potency among the metabolites tested, reaching 11.5% of aldosterone transactivation. The agonistic activity of 11beta-OH-P, 11alpha-OH-P and 17alpha-OH-P was 9, 5.1 and 4.1% respectively. At a concentration of 100 nmol/l, progesterone, 17alpha-OH-P and 20alpha-DH-P inhibit nearly 75, 40 and 35% of the transactivation by aldosterone respectively. All other progesterone metabolites tested demonstrate weaker affinity, and agonistic and antagonistic potency. CONCLUSIONS: The binding affinity for hMR and the agonistic and antagonistic activity diminish with increasing reduction of the progesterone molecule at C20, C17 and at ring A. We assume that progesterone metabolism to these compounds is a possible protective mechanism for hMR. 17alpha-OH-P is a strong hMR antagonist and could exacerbate mineralocorticoid deficiency in patients with congenital adrenal hyperplasia.

Asbestos fibers in parenteral medication.

The adequacy of current regulations for the control of particulate matter in injectable medicines has been brought into question by a recent television program which reported that asbestos fibers had been found in a number of such preparations. The fibers were identified as chrysotile, which occurs very widely as a secondary mineral in rocks, and is almost ubiquitous among minerals derived from natural erosion. Fibers are found in almost all drinking water and air samples unrelated to any contamination of fiber resulting from industrial exploitation. Because of this, even extreme laboratory precautions may fail to eliminate every fine fiber. A normal person living in an urban environment inhales about 10(5) asbestos fibers daily and ingests 10(10). There is evidence that a small proportion of these fibers regularly enters the circulation, and some fibers may be excreted in the urine. Elimination also occurs because retained chrysotile fibers fragment and disappear relatively quickly from human tissues, probably through macrophage action. Fiber length and dose are also important in disease causation. Established evidence on fiber length, durability, and quantitative exposure required for disease production does not indicate that the fibers reported to have been found in parenteral preparations constitute any hazard.

Carcinogenicity of the insulation wools: reassessment of the IARC evaluation.

In assessing the health evidence concerning man-made mineral fibers, the chemical composition, surface activity, durability, and size of fibers have to be taken into account. Special-purpose fine glass fibers need to be separated from the insulation wools (glass, rock, and slag wool). The epidemiological evidence is sufficient to conclude that there has been no mesothelioma risk to workers producing or using glass wool, rock wool, or slag wool. The epidemiological studies have been large and powerful, and they show no evidence of a cause-effect relationship between lung cancer and exposure to glass wool, rock wool, or slag wool fibers. There is some evidence of a small cancer hazard attached to the manufacturing process in slag wool plants 20 to 50 years ago, when asbestos was used in some products and other carcinogenic substances were present. However, this hazard is not associated with any index of exposure to slag wool itself. Animal inhalation studies of ordinary insulation wools also show that there is no evidence of hazard associated with exposure to these relatively coarse, soluble fibers. The evidence of carcinogenicity is limited to experiments with special-purpose fine durable glass fibers or experimental fibers, and only when these fibers are injected directly into the pleural or peritoneal cavity. Multiple chronic inhalation studies of these same special-purpose fine glass fibers have not produced evidence of carcinogenicity. It is suggested that the present IARC evaluation of the carcinogenic risk of insulation wools should be revised to Category 3: not classifiable as to carcinogenicity to humans.

Asbestos-related benign disease and cancer: symptoms and treatment.

Long lasting occupational exposure to asbestos dust may cause skin corns, benign pleural effusion, hyaline plaques of the parietal pleura, diffuse thickening of the pulmonary pleura, and asbestosis, i.e. diffuse interstitial pulmonary fibrosis. Malignant disorders include lung cancer and mesothelioma of the pleura, peritoneum and pericardium. In general, many years elapse from first exposure to the appearance of symptoms. Almost all these diseases are the result of dusty working conditions more than 20 years ago. In spite of the fact that the general public is invariably exposed to small amounts of the material, asbestos is not a public health problem. Even living in a building containing sprayed asbestos is calculated to produce a lifetime risk of death which is negligible. There is no evidence to indicate that ingested asbestos fibres represent a major health problem.

Liver metastasis in cancer of the stomach and its dependence on the histology of the primary tumor: an autopsy study on 102 cases.

The case records of 102 patients who had died of gastric cancer between 1975 and 1983 were evaluated. Special emphasis was given to an analysis of the metastatic liver involvement in relation to various histological classifications. The results show a strong preponderance of liver involvement by differentiated adenocarcinomas without intra- or extracellular mucin production, whereas signet ring cell carcinomas or adenocarcinomas with a major extracellular mucin production seem to avoid the liver. If the liver is being involved by the latter tumors, the degree of involvement remains low. Other relationships between certain histologies and the subsequent spread are briefly reported and compared with available data from the literature. The impact on adjuvant therapeutic strategies is discussed.

Occult papillary carcinoma of the thyroid with pulmonary lymphangitic spread diagnosed by lung biopsy.

Distant metastases from occult papillary carcinoma of the thyroid, which is defined as a tumor less than 15 mm in diameter, are extremely rare. A 21-year-old patient with miliary micronodular densities in both lungs is described, in whom pulmonary lymphangitic spread of occult papillary thyroid carcinoma was diagnosed by transthoracic lung biopsy.

[Synchronous occurrence of neoplasias of the thyroid gland and hyperthyroid nodular struma in an endemic area]. / Synchrones Auftreten von Neoplasien der Schilddrüse und hyperthyreoten Knotenstrumen im Endemiegebiet.

The simultaneous occurrence of hyperthyroidism and differentiated carcinoma of the thyroid gland is more frequent than previously assumed. In our endemic goiter region 16.5% of patients with thyroid carcinoma have hyperthyroidism and 1.8% of patients with hyperthyroidism have a thyroid carcinoma. The tumors are predominantly located in autonomous adenomas but are also found in cold nodules. Not only scintigraphically cold nodules but also warm and hot nodules must be suspected of malignancy. Consistent preoperative cytodiagnosis of all goiter nodules, including hot nodules, is therefore recommended. Surgical treatment of toxic multi-nodular goiters should be considered more often.

What every surgeon should know regarding asbestos-related disease.

Long-lasting occupational exposure to asbestos dust may cause pleural disease, asbestosis, bronchogenic carcinoma and mesothelioma. Many years elapse from first exposure to the appearance of symptoms. Almost all these diseases are the result of dusty working conditions 20-40 years ago. The pathological sequelae are usually irreversible and can progress after exposure ceases. There is no satisfactory treatment. Prevention is the only practical way. In spite of the fact that the general public is invariably exposed to small amounts of the material, asbestos is not a public health problem. Exemptions are the buildings not properly cared for containing sprayed asbestos. But even living in such buildings is calculated to produce a negligible risk of death. Asbestos-related diseases occur where long-lasting inhalation of high amounts of fine asbestos dust has occurred. There is no evidence to indicate that ingested asbestos fibers represent a major health problem. Industry is now replacing asbestos in many products by other fibers. Natural and synthetic organic materials used in fiber cement products are unable to reach the alveoli. They are not cancerogenic and there is no reason to believe that such fibers cause chronic pulmonary disease.

Prevention of fatal pulmonary embolism in patients with fractures of the neck of the femur.

Patients with fractures of the neck of the femur have an extremely high incidence of venous thrombosis and pulmonary emboli, if not receiving prevention with drugs. From a prospective, randomized multicenter trial comparing the effectiveness of two methods for the prevention of postoperative fatal pulmonary emboli, we analyzed those patients having been operated upon for a fracture of the neck of the femur. One hundred and seventy-two patients having had heparin-DHE prevention and 157 having had dextran prevention are compared with 150 patients in the control group and 165 patients who were given phenindione for anticoagulation orally. The data from the latter two groups stem from a study done in 1959 by Sevitt and Gallagher which for the first time established the value of oral anticoagulation for reducing pulmonary emboli. All three prophylactic methods reduce the incidence of pulmonary emboli to the same degree. The mortality associated with pulmonary emboli is 2 per cent in the phenindione group, 2.3 per cent in the heparin-DHE group and 3.8 per cent in the dextran group, in contrast with 10 per cent in the control group. Total mortality has been lowered significantly in all three groups as compared with the control group. Fatal pulmonary emboli were found only when prophylaxis had been stopped or was incomplete and were not found when prophylactic regimen was done properly. In 1980, the hospital stay was about one week shorter than in 1959.

[In which operations is antibiotic prevention carried out with only a a single dose? Results of a survey among chief physicians in general surgery in German-speaking Switzerland]. / Bei welchen Operationen wird eine Antibiotika-Prophylaxe mit nur einer Dosis durchgeführt? Ergebnisse einer Umfrage unter allgemeinchirurgischen Chefärzten der deutschsprachigen Schweiz.

We have been asking 108 surgeons in chief of the German speaking part of Switzerland in what operations they are giving an antibiotic prophylaxis. We wanted to know how far the application of the single-dose concept has been entering every day's practice in Switzerland. Its value has been proven in several prospective, randomized, controlled studies. Out of 84 valid questionnaires we could see that single-dose prophylaxis has not yet come into common use, although it is not only more reasonable but also less expensive than a prolonged course. Fortunately, already 90% of the surgeons are giving an antibiotic prophylaxis in colorectal surgery and 53% in biliary tract surgery. A majority of surgeons do not yet provide antibiotic prophylaxis in gastric surgery nor in appendectomies, where the single-dose prophylaxis is effective as well.

[The value of heparin-dihydergot in the prevention of thromboembolic complications]. / Wert von Heparin-Dihydergot zur Prophylaxe thromboembolischer Komplikationen.

57 papers dealing with the prevention of postoperative thromboembolic complications have been analyzed. They comprise 28 prospective, randomized, comparative studies using objective diagnostic techniques. 2 X 5000 IU daily of heparin-DHE lowers the incidence of deep vein thrombosis in general surgery, thoracic surgery and gynecology significantly better than 2 X 5000 IU heparin alone. In hip surgery 3 X 5000 IU heparin-DHE is more effective than the same amount of heparin alone. In the entire field of orthopedic surgery, heparin-DHE, in a dosage of 2 X 5000 IU, lowers the incidence of fatal pulmonary emboli just as well as dextran 70. With regard to prevention of deep vein thrombosis in general surgery, there is no statistically significant difference between prevention with 2 X 2500 IU heparin-DHE and 2 X 5000 IU heparin. 2 X 2500 IU heparin-DHE significantly lowers the incidence of bleeding complications in general surgery, as evaluated in double-blind studies and compared to 2 X 5000 IU heparin alone.

[Should antibiotic prevention be used in biliary tract surgery?]. / Soll man in der Gallenwegchirurgie eine Antibiotika-Prophylaxe machen?

A prospective, controlled, double-blind, randomized multicentre trial in Switzerland has been conducted to investigate the effectiveness of 5 g mezlocillin given during induction of anesthesia for prevention of infectious complications in biliary tract surgery. All adults undergoing elective or emergency surgery were included. Single-dose prevention reduces the incidence of wound infections from 10% to 4%, but does not reduce other kinds of infectious complications. The incidence of wound infections in the control group in Switzerland is only about half that in other countries. It is concluded that administration of single-dose mezlocillin to all patients in this type of surgery is justified. On the basis of risk factors it is impossible to predict reliably the patients who do not need protection.

[Perispinal anesthesia and subcutaneous administration of low-dose heparin-dihydergot for prevention of thromboembolism]. / Rückenmarksnahe Anaesthesie und subkutan verabreichtes low-dose Heparin-Dihydergot zur Thromboembolieprophylaxe.

The risk of haematoma formation in the spinal canal following spinal or epidural anaesthesia given in the presence of s.c. heparin-dihydroergotamine (DHE) for prevention of postoperative thromboembolic complications was examined. The data were obtained from a study that compared the effectiveness of s.c. heparin-DHE and i.v. Dextran 70. Heparin-DHE was administered two hours before anaesthesia and surgery and during the postoperative course. All patients underwent elective or emergency operations of the musculo-skeletal system. The s.c. heparin-DHE group consisted of 187 patients operated under spinal (82 patients) or epidural (105 patients, 66 of whom received an epidural catheter) anaesthesia. There were no clinical signs to suggest the presence of an epidural haematoma nor were there any neurological symptoms. The same was true in the dextran group. Specific neurological examinations were not carried out, but the clinical results were controlled by means of a questionnaire filled out by the patients 6 weeks postoperatively. We conclude that s.c. heparin-DHE or i.v. dextran 70 has been used safely in the presence of spinal or epidural anaesthesia in these patients.